Introducing Dendrosomal Nanocurcumin as a Compound Capable of in vitro Eliminating Undifferentiated Stem Cells in Cell Therapy Practices.

Abstract

One of the major obstacles needed to be overcome before using cell therapy for clinical purposes is the high probability of tumor formation in patients who receive the transplants, as undifferentiated stem cells (SCs) have the potential to form teratomas/teratocarcinoma in xenotransplants. In this study the ability of dendrosomal nanocurcumin (solublized curcumin using a biodegradable non-toxic nano-carrier) to affect undifferentiated/hazardous cell, and hence increasing the safety of cell therapy (particularly in diabetes type I) by mesenchymal stem cells (MSCs) was examined. The results showed that after completion of differentiation of human mesenchymal stem cells (hMSCs) into insulin producing cells (IPCs), the expression level of insulin increases, although there remains a minority of undifferentiated cells which still express nestin (gene which is expressed in progenitor stem cells of IPCs). It indicates the emergence of a heterogeneous population containing undifferentiated and differentiated cells. Furthermore our data demonstrated that the expression level of p53 decreases during differentiation of hMSCs into IPCs which implies a more favorable microenvironment for tumor formation following the transplantation of such a heterogeneous population. After treatment with dendrosomal nanocurcumin, nestin expression eliminated, however no significant effect on the expression and secretion of insulin was observed. Together our data shows that dendrosomal nanocurcumin have the ability to affect residual undifferentiated stem cells after the completion of differentiation of MSCs induced to differentiate into IPCs; while it exerts no significant harmful effect on the survival and function of differentiated cells. With regard to the obtained results in this study, exploiting dendrosomal nanocurcumin, after completion of induced differentiation of stem cells and prior to the transplantation step, can be suggested as a very efficient, safe and cost-effective method to eliminate the residual undifferentiated stem cells in cell therapy practices in order to considerably decrease the risk of tumor development following transplantation.